The Differences of Average Level Serum N Terminal Prob-Type Natriuretic Peptide (NTPROBNP) in Hypertension Patients with and without Left Ventricular Hypertrophy At Cardiology Outpatients Dr. Sardjito General Hospital Yogyakarta | Maulana | Acta Interna:
The Journal of Internal Medicine, Acta Interna, Volume 5, Number 1, June 2015: 1-8
The Differences of Average Level Serum N
Terminal Prob-Type Natriuretic Peptide (NTPROBNP) in Hypertension Patients with and
without Left Ventricular Hypertrophy At Cardiology
Outpatients Dr. Sardjito General Hospital
Yogyakarta
Gusti Hariadi Maulana1, Lucia Krisdinarti2, Hariadi Hariawan2
1
Speciality Training Program of Internal Medicine, Faculty of Medicine,
Universitas Gadjah Mada-Dr. Sardjito General Hospital
2
The Division of Cardiology, Department of Internal Medicine, Faculty of Medicine,
Universitas Gadjah Mada-Dr. Sardjito General Hospital
ABSTRAK
Abstrak. Hipertensi menyebabkan perubahan dalam struktur dan fungsi cardial sebagai pemicu
perubahan neurohormonal dan pembuluh darah pada hipertrofi jantung konsentris. Ekspansi
volume miosit atau peningkatan tekanan akan memicu sintesis pra-proBrain Natriuretic
Peptide (BNP) dalam miokardium ventrikel. Pre-proBNP akan dikonversi menjadi proBNP
sedangkan proBNP akan dikonversi ke dalam bentuk BNP dan N-terminal proBNP (NTproBNP).
Tujuan. Penelitian ini bertujuan untuk mengetahui perbedaan BT pro BNP pada pasien hipertensi tanpa
LVH dan pasien hipertensi dengan hipertrofi ventrikel kiri.
Metode. Desain penelitian adalah potong lintang di poliklinik kardiologi rawat jalan di Rumah
Sakit Dr. Sardjito Yogyakarta dari bulan Agustus 2009 sampai jumlah sampel terpenuhi. Untuk
menganalisis perbedaan antara dua kelompok pasien hipertensi menggunakan uji t-test untuk
distribusi nor mal, sedangkan untuk distribusi nor mal dianalisis dengan uji Mann-Whitney
U. Untuk menganalisis normalitas data dilakukan uji Kolmogorov-Smirnov. Perbedaan dua
kelompok pasien hipertensi dianggap signifikan jika p < 0,005 dengan interval kepercayaan 95%.
Hasil. Hasil penelitian menunjukkan 73 subyek penelitian dikelompokkan menjadi 2 kelompok yaitu
kelompok hipertensi tanpa LVH (31 subyek) dan dengan LVH (42 subyek) berdasarkan parameter
ekokardiografi (IVSD, LVPWd, LVIDd, LVM, dan LVMI) yang terdiri dari 24 laki-laki dan 49 perempuan.
Karakteristik dasar antara kelompok hipertensi dengan dan tanpa LVH tidak berbeda secara signifikan
baik dalam usia, BMI, tekanan darah, durasi karakteristik terapi hipertensi dari penggunaan obat-obatan
seperti ACEI, ARB, -blocker, CCB, spironolactone dan furosemide. Rerata tingkat NT proBNP pada
kelompok hipertensi tanpa LVH (46,60±45,51) dan hipertensi dengan kelompok hipertrofi ventrikel kiri
(201,60 ±192,30 ng/ml). Dari hasil uji Kolmogrov-Smirnov hasil bahwa distribusi data tidak normal
sehingga digunakan uji Mann-Whitney U, memperoleh perbedaan yang signifikan secara statistik.
Kesimpulan. Ada perbedaan yang signifikan dalam tingkat rata-rata serum NT proBNP pada pasien
hipertensi tanpa LVH dan pasien hipertensi dengan hipertrofi ventrikel kiri.
Kata kunci: hipertensi, hipertrofi ventrikel kiri (LVH), N-terminal proBrain natriuretik Peptida
1
Maulana et al.
ABSTRACT
Introduction. Hypertension cause changes in the structure and function of cardial as triggers
neurohormonal and vascular changes that concentric cardiac hypertrophy. Myocyte volume expansion or
increased pressure will trigger the synthesis of pre-proBrain Natriuretic Peptide (BNP) in the ventricular
myocardium. Pre-proBNP will be converted into proBNP and proBNP will be converted into the form
of BNP and N-terminal proBNP (NT proBNP).
Aim. This study aimed to determine differences in BT pro BNP in hypertensive patients without LVH and
hypertensive patients with LVH. The study design was cross-sectional in cardiology polyclinic`s outpatient
at Dr. Sardjito General Hospital Yogyakarta from August 2009 until the sample number is fulfilled.
Method. To analyze the difference between the two groups of hypertensive patients using the t-test for
normal distribution, while for abnormal distribution were analyzed with the Mann-Whitney U test. To
analyze the normality of data conducted by Kolmogorov-Smirnov. The differences of two groups of
hypertensive patients considered as significant if p < 0.005 with confidence interval of 95%.
Results. The results showed 73 study subjects grouped subjects into 2 groups: hypertensive subjects without
LVH (31 subjects) and with LVH (42 subjects) based on echocardiography parameters (IVSD, LVPWd,
LVIDd, LVM, and LVMI) consisting of 24 males and 49 females. The baseline characteristics between the
study groups of hypertensive subjects with and without LVH did not differ significantly either in age,
BMI, blood pressure, duration of hypertention therapeutic characteristics of the use of drugs such as
ACEI, ARB, -blocker, CCB, spironolactone and furosemide. Mean NT proBNP levels in hypertensive
group without LVH (46.60 ± 45.51) and hypertention with LVH group (201.60 ±192.30 ng/ml). From
the results of the Kolmogrov-Smirnov test result that the data distribution was not normal then used
Mann-Whitney U test, obtained a statistically significant differences.
Conclusion. There were significant differences in the mean levels of serum NT proBNP in hypertensive
patients without LVH and hypertensive patients with LVH.
Keywords: hypertension, left ventricular hypertrophy (LVH), N-terminal proBrain natriuretic Peptide
INTRODUCTION
World Health Organization (WHO)
reported that the systolic blood pressure
> 115 mmHg is responsible for 62% of
cerebrovascular disease and 49% of ischemic
heart disease with slight variations influenced
by gender. In the end that is not optimal
blood pressure is a risk factor for all-cause
mortality in the world.1
The prevalence of hypertension in
Indonesia in 2007 was 32.2%, and the highest
prevalence was found in the province of South
Kalimantan (39.6%), the lowest in West Papua
(20.1%). Socio-demographic factors were
found at risk for hypertension were age, gender,
education and employment, behavioral risk
factors are at risk for hypertension is first
2
ever smoking, alcohol consumption one last
month, one time consumption of caffeinated
beverages per day, and less physical activity,
risk factors physical risk for hypertension is
obesity and obesity abdominal.2
Essential hypertension is a major risk
factor for cardiovascular disease. Terminal
kidney disease incidence and prevalence of
heart failure also increases with the presence
of hypertension and blood pressure control
is not adequate.3,4,5
One of complications of hypertension
is the occurrence of ventricular hypertrophy
in the left (Left Ventricular Hypertrophy).
Left ventricular hypertrophy is marked by
hypertrophy concentric with hypertrophy
circumferential miofibril, contractility which
increased, an increase in thickness of wall
The Journal of Internal Medicine, Acta Interna, Volume 5, Number 1, June 2015: 1-8
ventricular, volume at the end of diastolic
are low, and disturbances relaxation (diastolic
dysfunction). On 30-50% individuals with
hypertension degrees I and II have left
ventricular relaxation disorders, and on
hypertension with degrees who more heavier,
2/3 of patients had abnormal relaxation left
ventricular.1,6 Expansion volume or pressure
myocytes which increased, resulted in the
stretch on ventricular wall so that triggering
synthesis of pre-proBrain Natriuretic Peptide
(BNP) in myocardium ventricle. Pre-proBNP
will later be converted into proBNP and
proBNP will converted into form of BNP
and N-terminal proBNP (NT proBNP).
The release of BNP and NT proBNP will
fix the relaxation myocardium and have an
important role in the responding an acute
increase volume ventricular with counteract
the effects vasoconstriction, retention, and
effects antidiuresis from system reninangiotensin which activated.7,8,9,10
LITERATURE REVIEW
Myocyte hypertrophy is a compensatory
response of increased afterload. Mechanical
and neurohor monal stimulation that
accompany hypertension may activate
myocardial cell growth, gene expression and
subsequently left ventricular hypertrophy.
Activation of the renin angiotensin system
causes the growth of cells and interstitial
matrix components, so that LVH is caused by
myocyte hypertrophy and myocyte imbalance
between myocardial interstitial skeletal
structure. Two major factors that trigger
hypertrophy is a biomechanical stress and
neurohumoral factors. According to the law
of Laplace, afterload induced increase in
systolic wall stress which offset an increase in
thickness of the ventricular wall of the heart.
Ion channels that are sensitive to the plasma
membrane indicated strain kardial myocytes.
The myocyte stretch induces the synthesis and
secretion of several growth factors including
insulin-like growth factor-I, angiotensin II and
endothelin I, and humoral factors is sufficient
to induce myocyte hypertrophy. Humoral
factors such as angiotensin II, aldosterone,
noradrenaline and endothelin directly induce
hypertrophy and status associated with
maladaptive processes to increase myocardial
fibrosis in ventricular hypertrophy.4
Remodeling is a change in the structure
(dimensions, mass, shape) and function of the
heart (called remodeling cardiac or ventricular)
as a result of hemodynamic load and cardiac
or injury associated with neurohormonal
activation. Remodeling is often divided into
physiological or pathological or classified
adaptive and maladaptive.4
Remodeling associated with cellular
changes including myocyte hypertrophy,
myocyte loss due to apoptosis or necrosis and
fibroblast proliferation and fibrosis. Although
the pathways and cellular involvement in
LV remodeling are not fully understood, the
molecular mechanisms at the level of the strain
is myocytes, there is increased production or
release of angiotensin II, norepinephrine
and endothelin, stimulates neurohormonal
changes in protein expression and myocyte
hypertrophy, increased angiotensin II,
aldosterone and stimulates cytokine synthesis
of collagen, causing fibrosis and extracellular
matrix remodeling. Reduction of nitric
oxide bioactivity effect on cell growth
and interstitial, at normal levels inhibit
remodeling. The end result of this research is
a pathological remodeling of cardiac damage
and increased neurohormonal activation.
3
Maulana et al.
Remodeling and myocardial changes play
a role in the pathogenesis of ventricular
arrhythmias.10
There are 3 major groups natriuretic
peptide, namely atrial natriuretic peptide
(ANP), B-type natriuretic peptide (BNP), and
C-type natriuretic peptide (CNP). Natriuretic
peptide is the characteristic biochemical
structure that consists of 17 amino acid ring
and a disulfide bond between two cysteine
molecules. B-type natriuretic peptide is also
called brain-type natriuretic peptide, is first
discovered in 1988 after isolated from pig
brain. Soon after the discovery, the BNP is a
cardiac hormone that comes from the heart.7,8
Atrial natriuretic peptide (ANP) and
B-type natriuretic peptide (BNP) is known as
an antagonist of the renin-angiotensin system.
C-type natriuretic peptide (CNP) is a new
member of natriuretic peptide group but the
difference of the main source in the vascular
endothelium. Unlike ANP and BNP, CNP
does not have direct natriuretic activity. This
is because CNP is a selective agonist for the
B-type natriuretic receptor whereas ANP and
BNP are selective for the A-type natriuretic
receptor.8
Major stimulus for the release of
BNP is increased myocardial stress due
to increase volume or pressure, increased
efforts mechanical (mechanical effort),
neurohormonal factors such as endothelin,
angiotensin II, adrenal steroids, inflammatory
cytokines, growth factors, prostaglandins,
thyroid hormone, and alpha-adrenergic
agents. Although the release of BNP occurs
under normal circumstances, increased
regulation could occur in a state of volume
overload.15
4
METHODS
This study was a cross-sectional study
were performed at the Cardiology outpatient
Dr. Sardjito General Hospital Yogyakarta and
Clinical Pathology Laboratory Dr. Sardjito
Yogyakarta. The study began in August 2009.
The study population was patients
attending Cardiology outpatient Dr. Sardjito
General Hospital Yogyakarta. As the sample
was hypertensive patients at the Cardiology
outpatient dr. Sardjito General Hospital
Yogyakarta diagnosed by JNC VII criteria.
Study subjects were recruited by consecutive
sampling method.
Inclusion criteria for the study were
all hypertensive patients who have been
diagnosed based on the criterias of JNC
VII 2003, in the treatment of hypertensive
patients, stated were willing to participate
in this study and signed a letter of informed
consent or informed consent of research
subjects as well as both medical measures
blood sampling.
Exclusion criteria included acute
coronary syndrome, primary valvular heart
disease, permanent arrhythmia, obesity,
diabetes mellitus, chronic renal disease,
hyperthyroidism, anemia, and stroke.
Estimates of the 24 samples in each group
were considered adequate to detect differences
in levels of NT-proBNP in hypertension with
left ventricular hypertrophy and without left
ventricular hypertrophy. Data presented in
the form of mean and standard deviations
(mean ± standard deviation). The difference
between the mean values of continuous data
were analyzed with the unpaired Student t-test
for normal distribution, while the distribution
was not normal was analyzed by the Mann-
The Journal of Internal Medicine, Acta Interna, Volume 5, Number 1, June 2015: 1-8
Table 1. Basic Characteristics of subject
Variabel
Age (years)
With left ventricle hypertrophy
n = 42
Without left ventricle hypertrophy
n = 31
P
50.70 ± 11.40
59.80 ± 12.20
0.7
Sex
0.8
n (%)
13 (31.00)
11 (35.50)
Female n (%)
29 (69.00)
20 (64.50)
IMT kg/m
25.00 ± 3.16
24.30 ± 3.40
0.3
TDS mmHg
145.00 ± 18.20
145.00 ± 14.20
0.9
TDD mmHg
88.00 ± 10.40
88.00 ± 8.40
0.9
HR x/mnt
76.70 ± 10.80
76.10 ± 5.50
0.7
Male
2
Hypertension
0.7
Stage I n (%)
40 (55.60%)
33 (44.40%)
Stage II n (%)
47 (65.00%)
26 (35.00%)
Long suffered (years)
9.50 ± 6.90
8.50 ± 6.70
0.5
Table 2. Therapy characteristics of subject
With left ventricle Hypertrophy
n = 42
Without left ventricle hypertrophy
n = 31
P
ACEI n (%)
24 (57.10)
12 (38.70)
0.1
ARB n (%)
11 (26.20)
13 (41.90)
0.2
Β-Blocker n (%)
9 (21.40)
5 (17.20)
0.7
CCB n (%)
9 (21.40)
7 (24.10)
0.7
Furosemid n (%)
26 (61.90)
10 (31.00)
0.1
4 (9.5)
1 (3.4)
0.6
Without drug (%)
8.00
10.00
1 drug (%)
64.00
60.00
2 drug (%)
20.00
20.00
3 drug (%)
8.00
1000
Variable
Spironolactone n (%)
Drug use
0.98
5
Maulana et al.
Table 3. Parameters used in measuring left ventricular hypertrophy
With left ventricle hypertrophy
n = 42
Without left ventricle hypertrophy
n = 31
EF % (Mean±SD)
65.50 ± 8.00
67.7 ± 6.30
0.2
IVSD mm (Mean±SD)
1.30 ± 0.20
1.0 ± 0.10
0.00
LVPWd mm(Mean±SD)
1.20 ± 0.10
1.0 ± 0.10
0.00
LVIDd mm (Mean±SD)
4.7 ± 0.50
4.3 ± 0.30
0.02
LVM g/m (Mean±SD)
250.50 ± 74.10
160.20 ± 27.00
0.00
LVMI g/m2(Mean±SD)
155.10 ± 40.70
100.0 ± 13.0
0.00
Variable
2
P
Table 4. Differences of level NT proBNP
Variable
With left ventricle
hypertrophy
Without left ventricle
hypertrophy
P
NT proBNP (pg/ml)
201.60 ± 192.30
46.6 ± 45.10
0.00 *
Exp : * Mann Whitney U test, significant if p < 0.05.
Whitney U test. Categorical data discrepancies
with Chi Square test. Data were presented with
95% confidence interval and P value> 0.05 was
statistically significant.
RESULT AND DISCUSSION
Obtained 73 subjects with hypertension
without left ventricular hypertrophy (31
subjects) and hypertension with left ventricular
hypertrophy (42 subjects). Study subjects
consisted of 24 (32.87%) men and 49 (67.13%)
were women.
Figure 1 is a table showing the suitability
2x2 echocardiography examination by 2
examiners. From the above calculation kappa
value of 0.69 is obtained, which means the
power of inter-observer agreement (interexaminer) is quite high (satisfactory or good
category).
Table 3 shows the parameters used in
measuring left ventricular hypertrophy in
subjects research.
6
Age factor does not affect the outcome
of the study between the two groups. Role in
the life of considerable geometric changes and
left ventricular mass, especially in patients
with essential hypertension often occurs in
the elderly, male gender, hypertension is severe
degrees of hypertension, has been suffering
from hypertension more than a year, in obese
patients and patients with DM.11
Gender factor has no effect in this
study because it was not found significant
differences (p=0.8). Women will be better
protected from cardiovascular disease and
hypertension due to differences in estrogen
and androgen hormone balance and also
associated with the RAS system primarily
AT2 receptor is expressed lower in male rats
that facilitate the occurrence of cardiovascular
disease and hypertension.12 But in this study
the age range most fall into menopause age.
Relationship of obesity and hypertension
complex, multifactorial mechanisms including
activation of the sympathetic system and
renin, insulin resistance, abnormal renal
The Journal of Internal Medicine, Acta Interna, Volume 5, Number 1, June 2015: 1-8
sodium regulation, and the possibility of
leptin resistance and natriuretic peptides.
Data from systolic and diastolic blood
pressure in both groups subjects not found a
significant difference (p=0.9) so that it can be
concluded that the effect of high blood pressure
on the outcome of research that NT proBNP
was similar in both groups of subjects.
Long suffered from hypertension between
the two groups were similar in this study. In
another study concluded that long hypertension
associated with left ventricular hypertrophy (p
The Differences of Average Level Serum N
Terminal Prob-Type Natriuretic Peptide (NTPROBNP) in Hypertension Patients with and
without Left Ventricular Hypertrophy At Cardiology
Outpatients Dr. Sardjito General Hospital
Yogyakarta
Gusti Hariadi Maulana1, Lucia Krisdinarti2, Hariadi Hariawan2
1
Speciality Training Program of Internal Medicine, Faculty of Medicine,
Universitas Gadjah Mada-Dr. Sardjito General Hospital
2
The Division of Cardiology, Department of Internal Medicine, Faculty of Medicine,
Universitas Gadjah Mada-Dr. Sardjito General Hospital
ABSTRAK
Abstrak. Hipertensi menyebabkan perubahan dalam struktur dan fungsi cardial sebagai pemicu
perubahan neurohormonal dan pembuluh darah pada hipertrofi jantung konsentris. Ekspansi
volume miosit atau peningkatan tekanan akan memicu sintesis pra-proBrain Natriuretic
Peptide (BNP) dalam miokardium ventrikel. Pre-proBNP akan dikonversi menjadi proBNP
sedangkan proBNP akan dikonversi ke dalam bentuk BNP dan N-terminal proBNP (NTproBNP).
Tujuan. Penelitian ini bertujuan untuk mengetahui perbedaan BT pro BNP pada pasien hipertensi tanpa
LVH dan pasien hipertensi dengan hipertrofi ventrikel kiri.
Metode. Desain penelitian adalah potong lintang di poliklinik kardiologi rawat jalan di Rumah
Sakit Dr. Sardjito Yogyakarta dari bulan Agustus 2009 sampai jumlah sampel terpenuhi. Untuk
menganalisis perbedaan antara dua kelompok pasien hipertensi menggunakan uji t-test untuk
distribusi nor mal, sedangkan untuk distribusi nor mal dianalisis dengan uji Mann-Whitney
U. Untuk menganalisis normalitas data dilakukan uji Kolmogorov-Smirnov. Perbedaan dua
kelompok pasien hipertensi dianggap signifikan jika p < 0,005 dengan interval kepercayaan 95%.
Hasil. Hasil penelitian menunjukkan 73 subyek penelitian dikelompokkan menjadi 2 kelompok yaitu
kelompok hipertensi tanpa LVH (31 subyek) dan dengan LVH (42 subyek) berdasarkan parameter
ekokardiografi (IVSD, LVPWd, LVIDd, LVM, dan LVMI) yang terdiri dari 24 laki-laki dan 49 perempuan.
Karakteristik dasar antara kelompok hipertensi dengan dan tanpa LVH tidak berbeda secara signifikan
baik dalam usia, BMI, tekanan darah, durasi karakteristik terapi hipertensi dari penggunaan obat-obatan
seperti ACEI, ARB, -blocker, CCB, spironolactone dan furosemide. Rerata tingkat NT proBNP pada
kelompok hipertensi tanpa LVH (46,60±45,51) dan hipertensi dengan kelompok hipertrofi ventrikel kiri
(201,60 ±192,30 ng/ml). Dari hasil uji Kolmogrov-Smirnov hasil bahwa distribusi data tidak normal
sehingga digunakan uji Mann-Whitney U, memperoleh perbedaan yang signifikan secara statistik.
Kesimpulan. Ada perbedaan yang signifikan dalam tingkat rata-rata serum NT proBNP pada pasien
hipertensi tanpa LVH dan pasien hipertensi dengan hipertrofi ventrikel kiri.
Kata kunci: hipertensi, hipertrofi ventrikel kiri (LVH), N-terminal proBrain natriuretik Peptida
1
Maulana et al.
ABSTRACT
Introduction. Hypertension cause changes in the structure and function of cardial as triggers
neurohormonal and vascular changes that concentric cardiac hypertrophy. Myocyte volume expansion or
increased pressure will trigger the synthesis of pre-proBrain Natriuretic Peptide (BNP) in the ventricular
myocardium. Pre-proBNP will be converted into proBNP and proBNP will be converted into the form
of BNP and N-terminal proBNP (NT proBNP).
Aim. This study aimed to determine differences in BT pro BNP in hypertensive patients without LVH and
hypertensive patients with LVH. The study design was cross-sectional in cardiology polyclinic`s outpatient
at Dr. Sardjito General Hospital Yogyakarta from August 2009 until the sample number is fulfilled.
Method. To analyze the difference between the two groups of hypertensive patients using the t-test for
normal distribution, while for abnormal distribution were analyzed with the Mann-Whitney U test. To
analyze the normality of data conducted by Kolmogorov-Smirnov. The differences of two groups of
hypertensive patients considered as significant if p < 0.005 with confidence interval of 95%.
Results. The results showed 73 study subjects grouped subjects into 2 groups: hypertensive subjects without
LVH (31 subjects) and with LVH (42 subjects) based on echocardiography parameters (IVSD, LVPWd,
LVIDd, LVM, and LVMI) consisting of 24 males and 49 females. The baseline characteristics between the
study groups of hypertensive subjects with and without LVH did not differ significantly either in age,
BMI, blood pressure, duration of hypertention therapeutic characteristics of the use of drugs such as
ACEI, ARB, -blocker, CCB, spironolactone and furosemide. Mean NT proBNP levels in hypertensive
group without LVH (46.60 ± 45.51) and hypertention with LVH group (201.60 ±192.30 ng/ml). From
the results of the Kolmogrov-Smirnov test result that the data distribution was not normal then used
Mann-Whitney U test, obtained a statistically significant differences.
Conclusion. There were significant differences in the mean levels of serum NT proBNP in hypertensive
patients without LVH and hypertensive patients with LVH.
Keywords: hypertension, left ventricular hypertrophy (LVH), N-terminal proBrain natriuretic Peptide
INTRODUCTION
World Health Organization (WHO)
reported that the systolic blood pressure
> 115 mmHg is responsible for 62% of
cerebrovascular disease and 49% of ischemic
heart disease with slight variations influenced
by gender. In the end that is not optimal
blood pressure is a risk factor for all-cause
mortality in the world.1
The prevalence of hypertension in
Indonesia in 2007 was 32.2%, and the highest
prevalence was found in the province of South
Kalimantan (39.6%), the lowest in West Papua
(20.1%). Socio-demographic factors were
found at risk for hypertension were age, gender,
education and employment, behavioral risk
factors are at risk for hypertension is first
2
ever smoking, alcohol consumption one last
month, one time consumption of caffeinated
beverages per day, and less physical activity,
risk factors physical risk for hypertension is
obesity and obesity abdominal.2
Essential hypertension is a major risk
factor for cardiovascular disease. Terminal
kidney disease incidence and prevalence of
heart failure also increases with the presence
of hypertension and blood pressure control
is not adequate.3,4,5
One of complications of hypertension
is the occurrence of ventricular hypertrophy
in the left (Left Ventricular Hypertrophy).
Left ventricular hypertrophy is marked by
hypertrophy concentric with hypertrophy
circumferential miofibril, contractility which
increased, an increase in thickness of wall
The Journal of Internal Medicine, Acta Interna, Volume 5, Number 1, June 2015: 1-8
ventricular, volume at the end of diastolic
are low, and disturbances relaxation (diastolic
dysfunction). On 30-50% individuals with
hypertension degrees I and II have left
ventricular relaxation disorders, and on
hypertension with degrees who more heavier,
2/3 of patients had abnormal relaxation left
ventricular.1,6 Expansion volume or pressure
myocytes which increased, resulted in the
stretch on ventricular wall so that triggering
synthesis of pre-proBrain Natriuretic Peptide
(BNP) in myocardium ventricle. Pre-proBNP
will later be converted into proBNP and
proBNP will converted into form of BNP
and N-terminal proBNP (NT proBNP).
The release of BNP and NT proBNP will
fix the relaxation myocardium and have an
important role in the responding an acute
increase volume ventricular with counteract
the effects vasoconstriction, retention, and
effects antidiuresis from system reninangiotensin which activated.7,8,9,10
LITERATURE REVIEW
Myocyte hypertrophy is a compensatory
response of increased afterload. Mechanical
and neurohor monal stimulation that
accompany hypertension may activate
myocardial cell growth, gene expression and
subsequently left ventricular hypertrophy.
Activation of the renin angiotensin system
causes the growth of cells and interstitial
matrix components, so that LVH is caused by
myocyte hypertrophy and myocyte imbalance
between myocardial interstitial skeletal
structure. Two major factors that trigger
hypertrophy is a biomechanical stress and
neurohumoral factors. According to the law
of Laplace, afterload induced increase in
systolic wall stress which offset an increase in
thickness of the ventricular wall of the heart.
Ion channels that are sensitive to the plasma
membrane indicated strain kardial myocytes.
The myocyte stretch induces the synthesis and
secretion of several growth factors including
insulin-like growth factor-I, angiotensin II and
endothelin I, and humoral factors is sufficient
to induce myocyte hypertrophy. Humoral
factors such as angiotensin II, aldosterone,
noradrenaline and endothelin directly induce
hypertrophy and status associated with
maladaptive processes to increase myocardial
fibrosis in ventricular hypertrophy.4
Remodeling is a change in the structure
(dimensions, mass, shape) and function of the
heart (called remodeling cardiac or ventricular)
as a result of hemodynamic load and cardiac
or injury associated with neurohormonal
activation. Remodeling is often divided into
physiological or pathological or classified
adaptive and maladaptive.4
Remodeling associated with cellular
changes including myocyte hypertrophy,
myocyte loss due to apoptosis or necrosis and
fibroblast proliferation and fibrosis. Although
the pathways and cellular involvement in
LV remodeling are not fully understood, the
molecular mechanisms at the level of the strain
is myocytes, there is increased production or
release of angiotensin II, norepinephrine
and endothelin, stimulates neurohormonal
changes in protein expression and myocyte
hypertrophy, increased angiotensin II,
aldosterone and stimulates cytokine synthesis
of collagen, causing fibrosis and extracellular
matrix remodeling. Reduction of nitric
oxide bioactivity effect on cell growth
and interstitial, at normal levels inhibit
remodeling. The end result of this research is
a pathological remodeling of cardiac damage
and increased neurohormonal activation.
3
Maulana et al.
Remodeling and myocardial changes play
a role in the pathogenesis of ventricular
arrhythmias.10
There are 3 major groups natriuretic
peptide, namely atrial natriuretic peptide
(ANP), B-type natriuretic peptide (BNP), and
C-type natriuretic peptide (CNP). Natriuretic
peptide is the characteristic biochemical
structure that consists of 17 amino acid ring
and a disulfide bond between two cysteine
molecules. B-type natriuretic peptide is also
called brain-type natriuretic peptide, is first
discovered in 1988 after isolated from pig
brain. Soon after the discovery, the BNP is a
cardiac hormone that comes from the heart.7,8
Atrial natriuretic peptide (ANP) and
B-type natriuretic peptide (BNP) is known as
an antagonist of the renin-angiotensin system.
C-type natriuretic peptide (CNP) is a new
member of natriuretic peptide group but the
difference of the main source in the vascular
endothelium. Unlike ANP and BNP, CNP
does not have direct natriuretic activity. This
is because CNP is a selective agonist for the
B-type natriuretic receptor whereas ANP and
BNP are selective for the A-type natriuretic
receptor.8
Major stimulus for the release of
BNP is increased myocardial stress due
to increase volume or pressure, increased
efforts mechanical (mechanical effort),
neurohormonal factors such as endothelin,
angiotensin II, adrenal steroids, inflammatory
cytokines, growth factors, prostaglandins,
thyroid hormone, and alpha-adrenergic
agents. Although the release of BNP occurs
under normal circumstances, increased
regulation could occur in a state of volume
overload.15
4
METHODS
This study was a cross-sectional study
were performed at the Cardiology outpatient
Dr. Sardjito General Hospital Yogyakarta and
Clinical Pathology Laboratory Dr. Sardjito
Yogyakarta. The study began in August 2009.
The study population was patients
attending Cardiology outpatient Dr. Sardjito
General Hospital Yogyakarta. As the sample
was hypertensive patients at the Cardiology
outpatient dr. Sardjito General Hospital
Yogyakarta diagnosed by JNC VII criteria.
Study subjects were recruited by consecutive
sampling method.
Inclusion criteria for the study were
all hypertensive patients who have been
diagnosed based on the criterias of JNC
VII 2003, in the treatment of hypertensive
patients, stated were willing to participate
in this study and signed a letter of informed
consent or informed consent of research
subjects as well as both medical measures
blood sampling.
Exclusion criteria included acute
coronary syndrome, primary valvular heart
disease, permanent arrhythmia, obesity,
diabetes mellitus, chronic renal disease,
hyperthyroidism, anemia, and stroke.
Estimates of the 24 samples in each group
were considered adequate to detect differences
in levels of NT-proBNP in hypertension with
left ventricular hypertrophy and without left
ventricular hypertrophy. Data presented in
the form of mean and standard deviations
(mean ± standard deviation). The difference
between the mean values of continuous data
were analyzed with the unpaired Student t-test
for normal distribution, while the distribution
was not normal was analyzed by the Mann-
The Journal of Internal Medicine, Acta Interna, Volume 5, Number 1, June 2015: 1-8
Table 1. Basic Characteristics of subject
Variabel
Age (years)
With left ventricle hypertrophy
n = 42
Without left ventricle hypertrophy
n = 31
P
50.70 ± 11.40
59.80 ± 12.20
0.7
Sex
0.8
n (%)
13 (31.00)
11 (35.50)
Female n (%)
29 (69.00)
20 (64.50)
IMT kg/m
25.00 ± 3.16
24.30 ± 3.40
0.3
TDS mmHg
145.00 ± 18.20
145.00 ± 14.20
0.9
TDD mmHg
88.00 ± 10.40
88.00 ± 8.40
0.9
HR x/mnt
76.70 ± 10.80
76.10 ± 5.50
0.7
Male
2
Hypertension
0.7
Stage I n (%)
40 (55.60%)
33 (44.40%)
Stage II n (%)
47 (65.00%)
26 (35.00%)
Long suffered (years)
9.50 ± 6.90
8.50 ± 6.70
0.5
Table 2. Therapy characteristics of subject
With left ventricle Hypertrophy
n = 42
Without left ventricle hypertrophy
n = 31
P
ACEI n (%)
24 (57.10)
12 (38.70)
0.1
ARB n (%)
11 (26.20)
13 (41.90)
0.2
Β-Blocker n (%)
9 (21.40)
5 (17.20)
0.7
CCB n (%)
9 (21.40)
7 (24.10)
0.7
Furosemid n (%)
26 (61.90)
10 (31.00)
0.1
4 (9.5)
1 (3.4)
0.6
Without drug (%)
8.00
10.00
1 drug (%)
64.00
60.00
2 drug (%)
20.00
20.00
3 drug (%)
8.00
1000
Variable
Spironolactone n (%)
Drug use
0.98
5
Maulana et al.
Table 3. Parameters used in measuring left ventricular hypertrophy
With left ventricle hypertrophy
n = 42
Without left ventricle hypertrophy
n = 31
EF % (Mean±SD)
65.50 ± 8.00
67.7 ± 6.30
0.2
IVSD mm (Mean±SD)
1.30 ± 0.20
1.0 ± 0.10
0.00
LVPWd mm(Mean±SD)
1.20 ± 0.10
1.0 ± 0.10
0.00
LVIDd mm (Mean±SD)
4.7 ± 0.50
4.3 ± 0.30
0.02
LVM g/m (Mean±SD)
250.50 ± 74.10
160.20 ± 27.00
0.00
LVMI g/m2(Mean±SD)
155.10 ± 40.70
100.0 ± 13.0
0.00
Variable
2
P
Table 4. Differences of level NT proBNP
Variable
With left ventricle
hypertrophy
Without left ventricle
hypertrophy
P
NT proBNP (pg/ml)
201.60 ± 192.30
46.6 ± 45.10
0.00 *
Exp : * Mann Whitney U test, significant if p < 0.05.
Whitney U test. Categorical data discrepancies
with Chi Square test. Data were presented with
95% confidence interval and P value> 0.05 was
statistically significant.
RESULT AND DISCUSSION
Obtained 73 subjects with hypertension
without left ventricular hypertrophy (31
subjects) and hypertension with left ventricular
hypertrophy (42 subjects). Study subjects
consisted of 24 (32.87%) men and 49 (67.13%)
were women.
Figure 1 is a table showing the suitability
2x2 echocardiography examination by 2
examiners. From the above calculation kappa
value of 0.69 is obtained, which means the
power of inter-observer agreement (interexaminer) is quite high (satisfactory or good
category).
Table 3 shows the parameters used in
measuring left ventricular hypertrophy in
subjects research.
6
Age factor does not affect the outcome
of the study between the two groups. Role in
the life of considerable geometric changes and
left ventricular mass, especially in patients
with essential hypertension often occurs in
the elderly, male gender, hypertension is severe
degrees of hypertension, has been suffering
from hypertension more than a year, in obese
patients and patients with DM.11
Gender factor has no effect in this
study because it was not found significant
differences (p=0.8). Women will be better
protected from cardiovascular disease and
hypertension due to differences in estrogen
and androgen hormone balance and also
associated with the RAS system primarily
AT2 receptor is expressed lower in male rats
that facilitate the occurrence of cardiovascular
disease and hypertension.12 But in this study
the age range most fall into menopause age.
Relationship of obesity and hypertension
complex, multifactorial mechanisms including
activation of the sympathetic system and
renin, insulin resistance, abnormal renal
The Journal of Internal Medicine, Acta Interna, Volume 5, Number 1, June 2015: 1-8
sodium regulation, and the possibility of
leptin resistance and natriuretic peptides.
Data from systolic and diastolic blood
pressure in both groups subjects not found a
significant difference (p=0.9) so that it can be
concluded that the effect of high blood pressure
on the outcome of research that NT proBNP
was similar in both groups of subjects.
Long suffered from hypertension between
the two groups were similar in this study. In
another study concluded that long hypertension
associated with left ventricular hypertrophy (p